Reference

Design

An uncontrolled prospective study. All participants received the same treatment.

Participants

Forty-two overweight women with polycystic ovarian syndrome (PCOS) were selected from the University of Modena’s Gynecological Endocrinology Center in Italy. Participants were included if they had polycystic ovarian morphology on ultrasonography, mild to severe hirsutism and/or acne, oligomenorrhea or amenorrhea, a body mass index (BMI) greater than 25.5 m/kg, and normal prolactin levels. Participants were excluded if they had any other endocrine disorder or if they were on any hormonal treatment in the last 6 months.

Study Medication and Treatment Protocol

Study participants were divided into 2 groups based on their baseline fasting insulin levels. Participants in group A (n=15) had insulin below 12 µU/mL; participants in group B (n=27) had insulin above 12 µU/mL. All participants took myo-inositol (2 grams) and folic acid (200 mcg) dissolved in water between 9 am and 11 am daily for 8 weeks. No dietary or lifestyle modifications to improve insulin sensitivity were recommended during the study.

Primary Outcome Measures

BMI, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, estradiol, progesterone, androstenedione, testosterone, dehydroepiandrosterone sulfate (DHEA-S), glucose, C-peptide, oral glucose tolerance, and insulin levels were measured at baseline and at 8 weeks. Insulin sensitivity was calculated as a glucose-to-insulin ratio since this has been shown to be a valid marker of insulin sensitivity in women with PCOS.1

Key Findings

After the 8-week myo-inositol treatment, there was a significant reduction in LH/FSH ratio, FSH, prolactin, androstenedione, testosterone, insulin, and BMI compared to baseline; there was also a significant increase in the glucose/insulin ratio (8.4±0.9 to 12.1±0.2, P<0.01). In consideration of baseline fasting insulin levels, myo-inositol treatment induced similar changes in both groups but only patients in group B demonstrated significant reduction in fasting insulin levels (20.3±1.8 to 12.9±1.8 µU/mL, P<0.00001). No side effects or adverse events were observed in any of the study participants; however, a prior study demonstrated that when myo-inositol was dosed at 12 grams per day, patients experienced gastrointestinal distress like nausea, diarrhea, and flatulence.2

Over the last decade, myo-inositol has been used more and more as a natural insulin sensitizer.

Practice Implications

PCOS is one of the most common endocrine disorders, affecting up to 20% of women of reproductive age.3 The diagnostic criteria for PCOS include chronic oligomenorrhea or anovulation, hyperandrogenism, and polycystic ovarian morphology.4 PCOS is associated with an increased risk of developing hypertension, dyslipidemia, type 2 diabetes, and heart disease.5–7 Insulin resistance is another common feature of PCOS in both overweight and lean women,8 and it is often treated with insulin sensitizers like metformin.9,10 Over the last decade, myo-inositol, an isomerized and dephosphorylated precursor of glucose-6-phosphate, has been used more and more as a natural insulin sensitizer. The role of myo-inositol in the pathophysiology of PCOS has been the focus of recent studies. It has been suggested that insulin resistance in PCOS women can be attributed to a deficiency of myo-inositol’s intracellular metabolites, D-chiro-inositol (DCI) and inositol-phosphoglycan (IPG), mediators of insulin action.11–14 It has also been postulated that patients with PCOS have a higher urinary clearance of DCI.15 In addition to its role in insulin sensitivity, DCI functions as an intracellular messenger in mammalian oocytes, playing a role in the follicular milieu, meiotic resumption, and oocyte maturation.16,17

Treating women with myo-inositol or DCI has been shown to reduce androgen levels, help restore ovulatory function, lower blood pressure, and decrease triglyceride levels.18,19 This study confirms prior studies that have shown that myo-inositol or DCI administration improves endocrine parameters and insulin sensitivity, more so in women with higher fasting insulin levels, defined by a fasting insulin level greater than 12 µU/mL.20 Although weight loss and dietary interventions are also known to improve insulin sensitivity and hyperandrogenism and restore ovation in women with PCOS, 21– 23 studies investigating the potentially additive benefit of combining lifestyle interventions with myo-inositol would be beneficial. Myo-inositol is a safe and effective natural medicine for improving insulin resistance and it should be recommended in conjunction with other positive lifestyle modifications for the management of PCOS and insulin resistance.

About the Author

Setareh Tais, ND, is a naturopathic doctor practicing general family medicine with a focus on integrative family medicine and reproductive health in Fresno, California. She received her doctorate of naturopathic medicine from Bastyr University, Kenmore, Washington, and completed a naturopathic family medicine residency program with additional training in reproductive endocrinology and infertility. She is the president of the California Naturopathic Doctors Association, a founding board member of the Endocrinology Association of Naturopathic Physicians, and a member of the American Association of Naturopathic Physicians. For more information about her practice, please visit www.fresnoholisticmedicine.com and for more information on naturopathic reproductive endocrinology, please visit www.endoanp.com.